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Marked microglial reaction in normal aging human substantia nigra: correlation with extraneuronal neuromelanin pigment deposits.
Acta Neuropathol. 2007 Oct; 114(4):419-24.AN

Abstract

Multiple reports have documented an age-related loss, estimated at about 10% per decade, of the pigmented neurons in the substantia nigra. This is associated with motor dysfunction, including bradykinesia, stooped posture and gait disturbance. As microglia are activated by cell death and neuromelanin pigment, we hypothesized that there should be a significant microglial reaction in normal aging human substantia nigra. Sections of substantia nigra from elderly subjects (N = 15; mean 81.3; SD 7.0) and younger subjects (N = 7; mean 30.3; SD = 8.7), all of which had no specific neurologically or neuropathologically defined disorders, were stained immunohistochemically for MHC Class II and the area occupied by microglia was quantified in substantia nigra pars compacta. All elderly subjects showed a pronounced microglial reaction in the substantia nigra, with frequent, intensely stained hypertrophic microglia, while immunoreactive nigral microglia were much less frequent in the younger subjects. Quantification showed that in older subjects, the percentage of substantia nigra area occupied by microglial bodies and processes was significantly greater than for younger subjects (mean 19.6 vs. 3.6; P = 0.005). Extraneuronal neuromelanin deposits were present in all the older subjects but were absent or rare in the younger subjects. The neuromelanin deposit abundance score in the older subjects correlated significantly with the area occupied by immunoreactive microglia. The marked microglial reaction in normal aging human substantia nigra, together with the previously reported 35-80% pigmented neuron loss, indicates the presence of a powerful pathologic process that may be additive with specific age-related neurodegenerative diseases, including Parkinson's disease.

Authors+Show Affiliations

Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ 85351, USA. thomas.beach@sunhealth.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17639428

Citation

Beach, Thomas G., et al. "Marked Microglial Reaction in Normal Aging Human Substantia Nigra: Correlation With Extraneuronal Neuromelanin Pigment Deposits." Acta Neuropathologica, vol. 114, no. 4, 2007, pp. 419-24.
Beach TG, Sue LI, Walker DG, et al. Marked microglial reaction in normal aging human substantia nigra: correlation with extraneuronal neuromelanin pigment deposits. Acta Neuropathol. 2007;114(4):419-24.
Beach, T. G., Sue, L. I., Walker, D. G., Lue, L. F., Connor, D. J., Caviness, J. N., Sabbagh, M. N., & Adler, C. H. (2007). Marked microglial reaction in normal aging human substantia nigra: correlation with extraneuronal neuromelanin pigment deposits. Acta Neuropathologica, 114(4), 419-24.
Beach TG, et al. Marked Microglial Reaction in Normal Aging Human Substantia Nigra: Correlation With Extraneuronal Neuromelanin Pigment Deposits. Acta Neuropathol. 2007;114(4):419-24. PubMed PMID: 17639428.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Marked microglial reaction in normal aging human substantia nigra: correlation with extraneuronal neuromelanin pigment deposits. AU - Beach,Thomas G, AU - Sue,Lucia I, AU - Walker,Douglas G, AU - Lue,Lih Fen, AU - Connor,Donald J, AU - Caviness,John N, AU - Sabbagh,Marwan N, AU - Adler,Charles H, Y1 - 2007/07/17/ PY - 2007/02/19/received PY - 2007/06/04/accepted PY - 2007/05/29/revised PY - 2007/7/20/pubmed PY - 2007/12/27/medline PY - 2007/7/20/entrez SP - 419 EP - 24 JF - Acta neuropathologica JO - Acta Neuropathol VL - 114 IS - 4 N2 - Multiple reports have documented an age-related loss, estimated at about 10% per decade, of the pigmented neurons in the substantia nigra. This is associated with motor dysfunction, including bradykinesia, stooped posture and gait disturbance. As microglia are activated by cell death and neuromelanin pigment, we hypothesized that there should be a significant microglial reaction in normal aging human substantia nigra. Sections of substantia nigra from elderly subjects (N = 15; mean 81.3; SD 7.0) and younger subjects (N = 7; mean 30.3; SD = 8.7), all of which had no specific neurologically or neuropathologically defined disorders, were stained immunohistochemically for MHC Class II and the area occupied by microglia was quantified in substantia nigra pars compacta. All elderly subjects showed a pronounced microglial reaction in the substantia nigra, with frequent, intensely stained hypertrophic microglia, while immunoreactive nigral microglia were much less frequent in the younger subjects. Quantification showed that in older subjects, the percentage of substantia nigra area occupied by microglial bodies and processes was significantly greater than for younger subjects (mean 19.6 vs. 3.6; P = 0.005). Extraneuronal neuromelanin deposits were present in all the older subjects but were absent or rare in the younger subjects. The neuromelanin deposit abundance score in the older subjects correlated significantly with the area occupied by immunoreactive microglia. The marked microglial reaction in normal aging human substantia nigra, together with the previously reported 35-80% pigmented neuron loss, indicates the presence of a powerful pathologic process that may be additive with specific age-related neurodegenerative diseases, including Parkinson's disease. SN - 0001-6322 UR - https://www.unboundmedicine.com/medline/citation/17639428/Marked_microglial_reaction_in_normal_aging_human_substantia_nigra:_correlation_with_extraneuronal_neuromelanin_pigment_deposits_ L2 - https://dx.doi.org/10.1007/s00401-007-0250-5 DB - PRIME DP - Unbound Medicine ER -